Covering for an endoprosthetic device and methods of using for aneurysm treatment

ABSTRACT

The present invention relates to covered endoprosthetic devices. Covered endoprosthetic devices comprise an endoprosthesis and a sheath. The sheath comprises a central portion and outer portions, wherein the central portion preferentially restricts or causes a restriction of blood flow. Blood flow can be reduced by the central portion of the sheath by varying the permeability of the sheath or by having projections on the sheath that slow blood flow. Permeability may be provided by perforations or holes in the material of the sheath or by varying the polymer structure that makes up the sheath itself. The outer portions of the sheath do not substantially reduce blood flow. Methods of using sheath-covered endoprosthetic devices of the invention to treat aneurysms, especially aneurysms in proximity to small perforator vessels or arteries, are also encompassed.

This application is a continuation-in-part application of U.S. patentapplication Ser. No. 10/952,360, filed Sep. 27, 2004, and also claimsthe benefit of priority of U.S. Provisional Application No. 60/673,304,filed Apr. 19, 2005, both of which are incorporated herein by referencein their entirety.

FIELD OF THE INVENTION

The present invention relates to a covering for endoprosthetic devices.Methods of using endoprosthetic devices covered by a sheath of theinvention to treat aneurysms are also encompassed. The coveringspreferentially restrict blood flow to the aneurysm while leavingsurrounding areas substantially unaffected. In specific embodiments,aneurysms in proximity to small perforator vessels or arteries aretreated using devices and methods of the invention.

BACKGROUND OF THE INVENTION

An aneurysm is a phenomenon in which the wall of a blood vessel,typically an artery, is abnormally dilated due to weakening of thevessel wall and a bulb or ball shaped space is created connected to thevessel by a neck. Depending upon where in the body the aneurysm islocated, a ruptured aneurysm may be fatal.

Until recently, the main treatment of intracranial ruptured andunruptured aneurysms had been to expose the aneurysm in a surgicalprocedure and to clip the neck of the aneurysm using surgical clips.These open surgical procedures carry a significant degree of morbidityand mortality. Further, some intracranial aneurysms are inaccessible toopen procedures due to their locations deep inside the brain tissue.

More recently, aneurysm repair devices have been used to prevent theaneurysm from getting larger and ultimately rupturing. One popular typeof minimally invasive treatment is a detachable coil (DC) which is awire that is packed into the aneurysm through a catheter and thendetached from the catheter. The goal of packing enough mass of this wireinto the aneurysm is to increase the resistance to flow into theaneurysm. The probability of aneurysm rupture is further reduced if theslow flow into the aneurysm cause the formation of a thrombus whichexcludes the aneurysm from even more flow. The many shortcomings of thisapproach include the unpredictable nature of the procedure (thus leavinga number of aneurysms exposed to significant flow), the high number ofcoils required (which adds to the length and cost of the procedure), andthe possible embolization of coils into distal vessels (therebyoccluding them). These problems are especially relevant during treatmentof aneurysms with wide necks (e.g., aneurysms having a wide connectionto the blood vessel).

Many practitioners have attempted to provide an endoprosthetic devicefor therapeutically treating aneurysms that does not require an openprocedure and whose success is not dependent on the configuration of theaneurysm. For example, there have been a number of proposals forplacement of an intraluminal graft bridging the aneurysm to isolate theaneurysmal sac from the active arterial duct. However, this method alsooccludes any small perforator arteries or vessel branches (both inletand outlet branches) in the area of the aneurysm and thus causes loss ofblood flow to the branches.

There is therefore a need in the art for an aneurysm repair device thathas good and predictable aneurysm-sealing characteristics while having aminimal effect on the distal vessel as well as small branching vesselsaround the neck of the aneurysm.

SUMMARY OF THE INVENTION

The present invention relates to coverings for endoprosthetic devices.Such endoprosthetic devices comprise an endoprosthesis and a coveredportion or sheath. The endoprosthesis is covered on all or part of itsouter surface by a sheath that comprises a central portion and outerportions. The sheath preferentially restricts or causes a restriction ofblood flow to the aneurysm while leaving blood flow to surrounding areas(e.g., small perforator vessels or arteries around the neck of theaneurysm) substantially unaffected. In one embodiment, blood flow to theaneurysm is restricted by varying the permeability of the sheath.Permeability (i.e., porosity) of the sheath may be provided byperforations or holes in the material of the sheath, polymer coatings onthe sheath, by varying the polymer structure that makes up the sheathitself, or by directing differential cell growth on the sheath.

In a specific embodiment, the sheath comprises a central portion that isless permeable to blood flow than the outer portions. As a result, bloodflow through the covered endoprosthesis can be controlled and varied asdesired. The central portion of the sheath may be less permeable toblood flow than the outer portions of the sheath, for example, by havingfewer and/or smaller perforations and/or a less porous structure and/orby having preferential cell growth than the outer portions.

In another embodiment, blood flow to the aneurysm is restricted byprojections on the sheath. In a specific embodiment, the sheathcomprises a central portion that has projections. The projections extendinto the aneurysm through its neck. Projections on the sheath in areasnot opposing the neck of the aneurysm are caught between the sheath andthe wall of the vessel and thus not extended. The projections serve toslow blood flow into the aneurysm and thus may promote thrombosis. Inthis embodiment, the projections are 0.5 mm-5.0 mm in length.Preferably, the projections are longer than the diameter of anyperforator vessel or artery in proximity to the aneurysm.

In another embodiment, the sheath comprises a central portion that hassubstantially the same permeability to blood flow as the outer portions.The permeability of the sheath is such that blood flow is allowed intoareas (such as perforator vessels) that have an out-flow but isrestricted to areas that do not have an out-flow (such as the aneurysm).In this embodiment, the sheath has a porosity in the range of 10-100micrometers.

The sheath may be attached to the endoprosthetic device permanently ortransiently. The sheath may be expandable such that, as an endoprothesisis delivered into the lumen of the sheath, the sheath will take on theexterior configuration of the endoprosthesis. The endoprothesis may beany endoprothesis known in the art. In preferred embodiments, theendoprosthesis is a stent.

The sheath may be generally cylindrical in shape and have a lumentherethrough. The variability in blood flow caused by the sheath may bein sections that extend around the entire circumference of the sheath.Alternatively, variability in blood flow caused by the sheath may be insections that are confined to smaller areas that do not extend aroundthe entire circumference of the sheath. In some embodiments, the sheathonly has a central portion.

Methods of using the endoprosthetic device of the invention, e.g., totreat aneurysms, are also encompassed by the present invention. In suchmethods, the covered endoprosthetic device is placed in the lumen of theblood vessel or artery in the area of the aneurysm and is positionedsuch that the central portion of the sheath is facing the aneurysm.Thus, blood flow is reduced in the aneurysm. The reduced speed andamount of blood flow to the aneurysm may trigger a thrombosis whichfurther excludes the aneurysm from blood pressure. This reduces the riskof aneurysm rupture.

Any aneurysm can be treated according to the methods of the invention.In one embodiment, the aneurysm is an intracranial aneurysm. Moreparticularly, the intracranial aneurysm may be in proximity to one ormore perforators. In embodiments where the aneurysm is in proximity toone or more perforators, blood flow obstruction to the perforators dueto the sheath-covered endoprosthesis is minimized by 1) placement of theouter portion of the sheath facing the perforators such that the centralsection, e.g., the portion that restricts blood flow, is facing the neckof the aneurysm while the outer sections, e.g., the portions that do notsubstantially restrict blood flow, face the perforators or 2) coveringthe endoprosthesis with a sheath that allows flow into areas that havean out-flow but restricts flow to areas that do not have an out-flow. Inthis way, blood flow into the aneurysm is eventually decreased oreliminated without critically affecting blood flow to any perforator inproximity to the aneurysm.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1B are schematic views of a sheath 1 in one embodiment of theinvention. In this embodiment, the size of the perforations is variedbetween the central portion 5 and the outer portions 6 of the sheath.The sections that dictate variability in blood flow permeability extendaround the circumference of the sheath and along its entire length. Theflattened sheath in (A) has been made into a cylinder in (B). The smallperforations of the central portion 5 extend around the entirecircumference of the sheath as can be seen in (B).

FIGS. 2A-2B are schematic views of another embodiment of the sheath 1 ofthe invention. Here, the number of perforations is varied between thecentral portion 5 and the outer portions 6 of the sheath. The sectionsthat dictate variability in blood flow permeability extend around thecircumference of the sheath and along its entire length. The flattenedsheath in (A) has been made into a cylinder in (B). The less denseperforations of the central portion 5 extend around the entirecircumference of the sheath as can be seen in (B).

FIGS. 3A-3B are schematic views of another embodiment of the sheath 1 inanother embodiment of the invention. In this embodiment, the size of theperforations is varied between the central portion 5 and the outerportions 6 of the sheath. The smaller perforations of the centralportion 5 are confined to a region that is smaller than the size of theentire middle part of the sheath. The flattened sheath in (A) has beenmade into a cylinder in (B). The smaller perforations of the centralportion 5 do not extend around the entire circumference of the sheath ascan be seen in (B).

FIGS. 4A-4B are schematic views of a sheath 1 in another embodiment ofthe invention. In this embodiment, the porosity of the polymer structurethat makes up the sheath itself is varied between the central portion 5and the outer portions 6 of the sheath. The sections that dictatevariability in blood flow permeability extend around the circumferenceof the sheath and along its entire length. The flattened sheath in (A)has been made into a cylinder in (B). The less permeable area of thecentral portion 5 extends around the entire circumference of the sheathas can be seen in (B).

FIGS. 5A-5B are schematic views of a sheath 1 in another embodiment ofthe invention. In this embodiment, the porosity of the polymer structurethat makes up the sheath itself is varied between the central portion 5and the outer portions 6 of the sheath. The less permeable area of thecentral portion 5 is confined to a region that is smaller than the sizeof the middle part of the sheath. The flattened sheath in (A) has beenmade into a cylinder in (B). The less permeable central portion 5 doesnot extend around the entire circumference of the sheath as can be seenin (B).

FIG. 6 is a schematic view of a sheath-covered endoprosthesis 9. Thesheath 1 is shown attached to a portion of a stent 10.

FIG. 7 is a schematic of a blood vessel with a lumen 11 with asheath-covered endoprosthesis 9 in place facing an aneurysm 12. Thecentral portion 5 of the sheath 1 is facing the neck of the aneurysmwhile the outer portions 6 of the sheath 1 are on either side of theneck of the aneurysm. The sheath-covered endoprosthesis 9 comprises astent 10 with a sheath 1 attached.

FIG. 8 is a schematic of a cross-sectional view taken through the planedesignated 13 in FIG. 7 of a blood vessel 14 and an aneurysm 12 with aendoprosthetic device 10 partially covered by a sheath 1 in the vessellumen 11. The sheath-covered endoprosthetic device is in place facingthe aneurysm 12. In this embodiment, the central portion 5 of the sheath1 is facing the neck of the aneurysm while the outer portions 6 arelocated circumferentially on the sides of the neck of the aneurysm. Theendoprosthesis 10 and sheath 1 are adjacent to the wall of the bloodvessel 14.

FIGS. 9A-9B is a schematic view of another embodiment of the inventionwhere an endoprosthesis 10 that is covered by a sheath 1 embedded with alayer of material 15 that promotes endothelialization. In this schematicview (A), the sheath 1 has a central portion with no outer portions.However, a sheath of this embodiment can have outer portions that arepermeable to blood flow and are not embedded with a layer of materialthat promotes endothelialization. In this embodiment, the porosity ofthe endoprosthesis 10 is varied by the preferential addition of a layerof endothelial cells on the layer of material 15 that promotesendothelialization. (B) An endoprosthesis 10 that has a polymer sheath19 with a layer of material 15 that promotes endothelialization embeddedin the central portion is depicted.

FIGS. 10A-10D show schematic views of another embodiment of theinvention where an endoprosthesis 10 is covered by a sheath 1 that hasprojections 16. In this schematic view (A), the sheath 1 has a centralportion with no outer portions. However, a sheath of this embodiment canhave outer portions that are permeable to blood flow and do not haveprojections that promotes thrombosis. (B) A schematic of across-sectional view of a blood vessel 14 and an aneurysm 12 with aendoprosthetic device 10 partially covered by a sheath 1 that hasprojections 16 in the vessel lumen 11 is depicted. The endoprostheticdevice is in place facing the aneurysm 12. In this embodiment, theprojection-bearing portion of the sheath is facing the neck of theaneurysm. The projections 16 extend into the neck of the aneurysm 12 butare caught between the sheath 1 and the wall of the blood vessel 14 (andthus not extended) in areas that are not opposing the neck of theaneurysm 12. (C) An endoprosthesis 10 that has a polymer sheath 19 withprojections 16 in the central portion is depicted. (D) A schematic of ablood vessel 14 with an endoprosthesis 10 that has a polymer sheath 19with projections 16 in the central portion in place facing an aneurysm12. In this embodiment, the projection-bearing portion of the sheath isfacing the neck of the aneurysm. The projections 16 extend into the neckof the aneurysm 12 but are caught between the sheath and the wall of theblood vessel 14 (and thus not extended) in areas 17 that are notopposing the neck of the aneurysm 12. The small perforator vessels orarteries 18 in the proximity of the aneurysm are not effected by theprojections.

FIGS. 11A-11 B are pictures of an endoprosthesis 10 covered with asheath 1 of substantially uniform permeability to blood flow in thecentral 5 and outer 6 portions. The sheath 1 is made of a polymer withporosity in the range of 10-100 micrometers over its entire length. Thesheath-covered endoprosthetic device 9 (A) and a 500× magnification ofthe sheath 1 (B) are shown

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description should be read with reference to thedrawings in which like elements in different drawings are numberedidentically. The drawings, which are not necessarily to scale, depictselected embodiments and are not intended to limit the scope of theinvention.

Examples of constructions, materials, dimensions, and manufacturingprocesses are provided for selected elements. All other elements employthat which is known to those skilled in the field of the invention.Those skilled in the art will recognize that many of the examplesprovided have suitable alternatives that may also be used.

The covered endoprosthetic devices of the invention are covered with asheath. The sheath preferentially restricts or causes a restriction ofblood flow to the aneurysm while leaving blood flow to surrounding areas(e.g., small perforator vessels or arteries around the neck of theaneurysm) substantially unaffected. In one embodiment, blood flow to theaneurysm is restricted by varying the permeability of the sheath (e.g.,see FIGS. 1A-1B, 2A-2B, 3A-3B, 4A-4B, 5A-5B and 9A-9B). In anotherembodiment, blood flow to the aneurysm is slowed by projections from thesheath that may result in thrombosis (e.g., see FIGS. 10A-10D).

A sheath of the present invention may cover all or a part of anendoprosthetic device. In some embodiments, the sheath comprises acentral portion flanked by outer portions. In other embodiments, thesheath comprises only a central portion. The central portion of thesheath restricts or causes a restriction of blood flow to the aneurysm.This reduced blood flow to the aneurysm can be caused by the centralportion having 1) a low permeability to blood flow (caused by, e.g.,small or no perforations in the material of the sheath, polymer coatingson the sheath, the polymer structure of the material of the sheathitself, or cell growth on the sheath) or 2) projections that extend intothe neck of the aneurysm. The outer portions of the sheath allowsufficient blood flow so that any perforator vessel or artery facing anouter portion will not be substantially affected. The outer portions mayor may not allow the same amount of blood flow when compared to eachother, however, the outer portions will preferably allow a greateramount of blood flow than the central portion.

In some embodiments, the central portion is uniform around the entirecircumference of the sheath (see, e.g., FIGS. 1A-1B, 2A-2B, 4A-4B,9A-9B, and 10A-10D). In other embodiments, the central portion is notuniform around the entire circumference of the sheath (see, e.g., FIGS.3A-3B and 5A-5B). In such embodiments, there is a section of the centralportion that restricts or causes a restriction of blood flow which canbe positioned opposite the neck of aneurysm. Other sections of thecentral portion that do not substantially restrict blood flow arepositioned opposite small perforator vessels or arteries around the neckof the aneurysm without compromising blood flow to them. These sectionsof the central portion that do not substantially restrict blood flow mayor may not have the same permeability to blood flow that the outerportions.

The sheath may also have multiple “central” portions, for example, whenthe sheath is intended to cover multiple aneurysms which are closeenough in proximity to be covered with a single device. In such anembodiment, the central portions may be positioned to cover suchaneurysms, while outer portions may preferably be located to surroundthe central portions. It is understood that many of the embodimentsdescribed herein may be adapted to accommodate multiple centralportions.

The sheath may further include a proximal opening and a distal opening.In its non-distended configuration, the sheath may generally form acylinder. The sheath may be attached to the endoprosthesis by any methodknown in the art, providing that the method of attachment is appropriatefor the materials used to make the sheath and endoprosthesis. In oneembodiment, an adhesive bond is used to attach the sheath to theendoprosthesis. Such a bond may be engineered to detach at any desiredtime or at a desired force. The adhesive bond may be formed with anymedically approved adhesive.

In one embodiment, the endoprosthesis is a stent. Any stent can becovered by the sheath of the invention to make a sheath-covered stent.The skilled artisan is well aware of the many stents available in theart. Any such stent may be amenable to use in the instant invention. Thestents may be self-expanding or may be balloon-expandable stents. Anymethod can be used to attach the sheath to the stent, providing that themethod of attachment is appropriate for the materials used to make thestent and sheath. In one embodiment, the sheath is attached to the stentusing an adhesive bond. The sheath may be attached to the stentpermanently or transiently.

FIGS. 1A and 1B illustrate the sheath 1 which makes the covered portionof the endoprosthetic device. The solid portion 2 of the sheath can bemade of any material known in the art that has properties that allowsthe covered endoprosthetic device to be capable of getting to theaffected area. For example, sheath 1 may be made of an elastomer orother highly compliant polymer. Such polymers may include latex,styrenic block copolymers such as SBS and SEBS made by Shell under tradename Kraton, polyether-ester block copolymers (COPE) for co-polyestersmade by DuPont under the trade name of Hvtrel, thermoplastic polyamideelastomers (PEBA) made by Atochem under the trade name of Pebax, andthermoplastic polyurethane elastomer (TPUR) made by Dow under the tradename Pellathane, or thermoplastic polyolefin elastomers (TPOs). Thematerials may themselves be biocompatible or they may be plated with abiocompatible material. Additionally, the materials may or may not bebiodegradable. Similarly, the sheath may be made of any textile, film ormaterial such as DACRON, polyester, polyethylene terephthalate (PET),polytetrafluoroethylene (PTFE), or any other suitable material.Preferably the material is compliant.

In embodiments where the sheath has differential permeability, thedifferential permeability may be provided by the selection of specificmaterials to make up the sheath. Many permeable materials are known tothe skilled artisan and their use in the sheath of the invention isencompassed herein. The terms permeability, porosity, and perforations(density thereof) are used interchangeably herein.

In some embodiments, the sheath 1 has perforations 3, 4 that allow someblood to flow through the sheath, i.e., porosity. Although circularperforations 3, 4 are shown in FIGS. 1A-1B, the perforations in thesheath may be of any shape. The perforations in the sheath can be all ofthe same shape or they may be more than one shape. In the embodimentillustrated in FIGS. 1A-1B, the size of the perforations vary in thesheath 1. For example, the central portion 5 of the sheath may havesmaller perforations than those in the outer portions 6 (e.g., as shownby comparison of hole or perforation 4 with hole 3). Although theperforations in the central portion 5 and the outer portions 6 are shownin FIGS. 1A-1B as homogenous in size, the perforations in the sheath ofthe invention may be of varied size within a portion.

The perforations in the outer portions 6 are preferably large enough toallow sufficient blood flow through the sheath such that any perforatorvessel or artery facing the outer portion would not be substantiallyaffected. The outer portions 6 may or may not have the same sizeperforations when compared to each other, however, each of the outerportions will have an average hole size that is greater than the averagehole size of the central portion.

The perforations in the central portion 5 are of a size and/or porosityto allow for some restricted permeability through the sheath such thatan aneurysm facing a central portion will have reduced blood flow andpressure as compared to the amount of blood flow and pressure in theabsence of the sheath. In this embodiment, other parts of the sheathcontain larger perforations to provide more permeability. The size ofthe perforations can be empirically determined by the skilled artisanbased on physiological factors such as type and size of the vessel andsize/morphology of the aneurysm being treated.

In one embodiment, the porosity of the central portion is uniform aroundthe entire circumference of the sheath. In a specific embodiment,depicted in FIGS. 1A-1B, the sheath has a uniform porosity throughoutthe entire central portion. In another specific embodiment, a sheath hasheterogeneous porosity in the central portion so long as the overallporosity of this portion is uniform around the entire circumference ofthe sheath.

Another embodiment of the invention is illustrated in FIGS. 2A-2B. Inthis embodiment, the sheath 1 has perforations 7, 8 to allow somepermeability in the sheath. The perforations 7, 8 are less dense in thecentral portion 5 than in the outer portions 6. The density ofperforations in the sheath is such that there is overall lesspermeability in the central portion than the outer portion of thesheath.

The density of the perforations in the outer portions 6 is high enoughto allow sufficient blood flow so that any perforator vessel or arteryfacing an outer portion will not be substantially affected. The outerportions may or may not have the same density of perforations (i.e.,porosity) when compared to each other, however, the outer portions willpreferably have a porosity that is greater than the porosity of thecentral portion 5.

Although perforations 7, 8 are of the same size in FIGS. 2A-2B, theperforations in the sheath may be of different sizes and/or shapes. Insome embodiments, it may be preferable to combine the embodiments ofFIGS. 1A-1B and 2A-2B to provide a sheath having a plurality ofperforations of varying size in the outer portions, and fewer and/orsmaller openings in the central portions of the sheath.

In another embodiment, the porosity of the central portion is uniformaround the entire circumference of the sheath. In a specific embodiment,depicted in FIGS. 2A-2B, the sheath has uniform-sized perforations inthe central portion. In another specific embodiment, a sheath hasheterogeneous-sized perforations in the central portion, however, theoverall porosity of the central portion is uniform around thecircumference of the sheath.

Another embodiment of the invention is illustrated in FIGS. 3A-3B. Inthis embodiment, the sheath 1 has variable-sized perforations to allowvariable permeability in the sheath. The central portion 5 has adecreased porosity than either of the outer portions 6. However, theporosity of the central portion 5 is not uniform around the entirecircumference of the sheath in this embodiment. The region of decreasedporosity in the central portion 5 is conferred by an area that hasperforations that are smaller in size than those of the outer portions6. This region is confined to an area that is smaller than the entirecentral portion of the sheath and thus does not continue around theentire circumference of the sheath. The remainder of the central portionhas a porosity that is substantially similar to that of the outerportions.

Although FIGS. 3A-3B depict a central portion with a region of decreasedporosity conferred by the presence of an area of smaller perforations,any means may be used to decrease porosity. For example, the region ofdeceased porosity in the central portion can be conferred by havingperforations that are less densely spaced than in the outer portions.

Another embodiment of the invention is illustrated in FIGS. 4A-4B. Inthis embodiment, the sheath 1 has a central portion 5 that as decreasedporosity compared to the outer portions 6 due to a varying polymerstructure that makes up the material of the sheath itself. In oneembodiment, the one or more polymers that make up the central portionare different (e.g., provide decreased porosity) than the one or morepolymers that make up the outer portions. In another embodiment, the oneor more polymers that make up the central portion are the same as theone or more polymers that make up the outer portions. In such anembodiment, the physical construction of different regions of the sheathmay differ. For example, as depicted in FIGS. 4A-4B, the one or morepolymers may be woven or braided in a tighter manner in the centralportion than in the outer portions in order to confer differentporosities.

In this embodiment, the porosity of the central portion may be uniformaround the entire circumference of the sheath.

Another embodiment of the invention is illustrated in FIGS. 5A-5B. Inthis embodiment, the sheath 1 has a central portion 5 that as decreasedporosity compared to the outer portions 6 due to a varying polymerstructure that makes up the material of the sheath itself as describedsupra for FIGS. 4A-4B. Although, the porosity of the central portion 5is overall decreased compared to the outer portions 6, the centralportion does not have a uniform porosity around the entire circumferenceof the sheath in this embodiment. The region of decreased porosity inthe central portion 5 is either made of a polymer that is different(e.g., has decreased porosity) or constructed differently (e.g., moretightly woven or braided) than the polymer that makes up the rest ofsheath. This region is confined to an area that is smaller than theentire middle part of the sheath. The remainder of the middle part has aporosity that is substantially similar to that of the outer portions.

FIG. 6 illustrates a schematic view of a sheath-covered endoprostheticdevice 9. The sheath 1 is shown covering a portion of an endoprosthesis10. Although the sheath shown depicts the sheath of FIGS. 3A-3B, anyembodiment of the sheath can be used to cover the endoprosthetic device.The sheath 1 is shown covering only a portion of the endoprostheticdevice 9. In other embodiments, it may be preferable for the sheath tocover more of the endoprosthesis up to and including the entire lengthof the endoprosthesis.

In some embodiments, the central portion of the sheath has a uniformporosity around the entire circumference of the sheath (e.g., FIGS.1A-1B, 2A-2B, and 4A-4B). In such embodiments, the uniform porosity ofthe central portion is decreased as compared to the porosity of theouter portions. In other embodiments, the region of decreased porosityis confined to an area that is smaller than the entire central portionof the sheath (e.g., FIGS. 3A-3B and 5A-5B). The remainder of thecentral portion has a porosity that is substantially similar to that ofthe outer portions. In such embodiments, the region of decreasedporosity in the central portion is present only on the side of thesheath that faces the aneurysm (e.g., one sixth, a quarter, a third, ora half of the circumference of the stent). This embodiment of asheath-covered stent is useful when there is a perforator on the side ofthe vessel opposite the aneurysm that would suffer from the decreasedpermeability that occurs in the central portion of the sheath.

FIG. 7 illustrates a sheath-covered endoprosthetic device 9 positionedin the lumen of a blood vessel 11 that has an aneurysm 12. Thesheath-covered endoprosthesis 9 is placed inside the lumen 11 of theblood vessel by a method known in the art. The sheath-coveredendoprosthesis 9 is positioned such that the central portion of thesheath 1 is facing the aneurysm 12. When placed appropriately, thecentral portion 5 of the sheath is facing the neck of the aneurysm whileone or more outer portions 6 may be positioned beyond the neck of theaneurysm. In FIG. 7, the outer portions are positioned longitudinallydistal and proximal to the neck of the aneurysm.

Any means known in the art can be used to locate the affected area(e.g., the lumen of a blood vessel or artery proximal to an aneurysm)and monitor the placement of the sheath-covered endoprosthesis. Inpreferred embodiments, the affected area is identified by diagnosticmethods known in the art, i.e., MRI or angiography.

FIG. 8 illustrates a cross-sectional view of a endoprosthetic device 10covered by a sheath 1 positioned in the lumen 11 of a blood vessel 14that has an aneurysm 12. The stent 10 is positioned in the lumen 11 ofthe blood vessel 14 such that the central portion 5 of the sheath 1 isfacing the area of the blood vessel with the aneurysm 12. In thisembodiment, the central portion 5 of the sheath is facing the neck ofthe aneurysm while the outer portions 6 are circumferentially located oneither side of the neck of the aneurysm. Thus, any perforator vessels inthe proximity to the aneurism will not have their blood flowsubstantially impeded.

FIGS. 9A-9B illustrate an endoprosthesis 10 that is covered by a sheath1 embedded with a layer of material 15 that promotes endothelialization.In this embodiment, the porosity of the endoprosthesis 10 is varied bythe eventual preferential addition of a layer of endothelial cells onthe layer of material 15 that promotes endothelialization. In someembodiments, the layer of material that promotes endothelialization canbe added to a central portion of another sheath of the invention (e.g.,as shown in any of FIGS. 1A-1B, 2A-2B, 3A-3B, 4A-4B, 5A-5B, 10A-10D and11A-11B) to further slow blood flow. Such an embodiment is depicted inFIG. 9B where the layer of material that promotes endothelialization isembedded in the polymer sheath of FIGS. 11A-11B.

The layer of material that promotes endothelialization comprises a firstmolecule capable of interacting with a second molecule that is on thesurface of an endothelial cell or its progenitor cell. Interactionsbetween first and second molecules direct the endothelial cells or theirprogenitors to adhere to the sensor. Non-limiting examples of firstmolecules are antibodies or antigen binding fragments thereof, smallmolecules, and extracellular matrix molecules.

In one specific embodiment, layer of material that promotesendothelialization. comprises one or more antibodies or antigen bindingfragments thereof. The antibody or antigen binding fragment thereofspecifically binds to or interacts with an antigen on the cell membraneor cell surface of endothelial cells and/or their progenitor cells thusrecruiting the cells from circulation and surrounding tissue to thesheath. The cell membrane or cell surface antigens to which theantibodies specifically bind are specific for the desired cell type(e.g., only or primarily found on endothelial cells or their progenitorcells). Several non-limiting examples of antibodies or antigen bindingfragments thereof useful in the present invention are directed to thefollowing antigens: e.g., vascular endothelial growth factor receptor-1,-2 and -3 (VEGFR-1, VEGFR-2 and VEGFR-3 and VEGFR receptor familyisoforms), Tie-1, Tie-2, Thy-1, Thy-2, Muc-18 (CD146), stem cellantigen-1 (Sea-1), stem cell factor (SCF or c-Kit ligand), VE-cadherin,P1H12, TEK, Ang-1, Ang-2, HLA-DR, CD30, CD3I, CD34, CDw90, CD117, andCD133. Alternatively, cell membrane or surface antigens to which theantibodies specifically bind may not exclusively be found on the desiredcell type, e.g., the cell membrane or surface antigens are found onother cells in addition to endothelial cells or their progenitor cells.In such embodiments, it may be preferable to use a mixture of antibodiesthat specifically bind to the non-specific cell membrane or surfaceantigens such that the profile of antigens recognized is unique to thedesired cell type, e.g., the cell membrane or surface antigensspecifically bound to by the mixture of antibodies are only or primarilyfound in that combination on endothelial cells and/or their progenitorcells.

In another specific embodiment, the layer of material that promotesendothelialization comprises one or more small molecules that bind oneor more ligands on the cell membrane or cell surface of the desiredcell. The small molecule recognizes and interacts with a ligand on anendothelial cell or its progenitor cell to immobilize the cell on thesurface of the sensor to form a layer of endothelial cells. Smallmolecules that can be used in the methods of the invention include, butare not limited to, inorganic or organic compounds; proteinaceousmolecules, including, but not limited to, peptides, polypeptides,proteins, modified proteins, or the like; a nucleic acid molecule,including, but not limited to, double-stranded DNA, single-stranded DNA,double-stranded RNA, single-stranded RNA, or triple helix nucleic acidmolecules, or hybrids thereof; fatty acids; or saccharides. Smallmolecules can be natural products derived from any known organism(including, but not limited to, animals, plants, bacteria, fungi,protista, or viruses) or may be one or more synthetic molecules. In oneembodiment, a small molecule for use in methods of the invention is alectin. A lectin is a sugar-binding peptide of non-immune origin whichbinds the endothelial cell specific lectin antigen (Schatz et al., 2000,Biol Reprod 62: 691-697). In other embodiments, small molecules thathave been created to target various endothelial and/or progenitor cellsurface receptors can be used in the methods of the invention. Forexample, VEGF receptors can be bound by SU11248 (Sugen Inc.) (Mendel etal., 2003, Clin Cancer Res. 9:327-37), PTK787/ZK222584 (Drevs et al.,2003, Curr Drug Targets 4:113-21) and SU6668 (Laird et al., 2002, FASEBJ. 16:681-90) while alpha v beta 3 integrin receptors can be bound bySM256 and SD983 (Kerr et al., 1999, Anticancer Res. 19:959-68).

In another specific embodiment, the layer of material that promotesendothelialization comprises one or more extracellular matrix (ECM)molecules to which endothelial cells and/or their progenitor cellsnaturally adhere. Examples of ECM molecules for use in accordance withthe present invention are basement membrane components, such as, forexample, collagen, elastin, laminin, fibronectin, vitronectin, as wellas basement membrane preparations, heparin, and fibrin.

The layer of material that promotes endothelialization may optionallycomprise a compound that promotes the survival, accelerates the growth,or causes or promotes the differentiation of endothelial cells and/ortheir progenitor cells. Any growth factor, cytokine or the like whichstimulates endothelial cell survival, proliferation and/ordifferentiation can be used in the methods of the invention. Compoundsused in the methods of the invention can be specific for endothelialcells including, but not limited to, angiogenin 1, angiogenin 2,platelet-derived growth factor (PDE-CGF), vascular endothelial cellgrowth factor 121 (VEGF 121), vascular endothelial cell growth factor145 (VEGF 145), vascular endothelial cell growth factor 165 (VEGF 165),vascular endothelial cell growth factor 189 (VEGF 189), vascularendothelial cell growth factor 206 (VEGF 206), vascular endothelial cellgrowth factor B (VEGF-B), vascular endothelial cell growth factor C(VEGF-C), vascular endothelial cell growth factor D (VEGF-D), vascularendothelial cell growth factor E (VEGF-E), vascular endothelial cellgrowth factor F (VEGF-F), proliferin, endothelial PAS protein 1, andleptin. Compounds used in the methods of the invention can benon-specific for endothelial cells including, but not limited to, basicfibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF),fibroblast growth factors 3-9 (FGF 3-9), platelet-induced growth factor(PIGF), transforming growth factor beta 1 (TGFβ1), transforming growthfactor alpha (TGFα), hepatocyte growth factor scatter factor (HGF/SF),tumor necrosis factor alpha (TNFα), osteonectin, angiopoietin 1,angiopoietin 2, insulin-like growth factor (ILGF), platelet-derivedgrowth factor AA (PDGF-AA), platelet-derived growth factor BB (PDGF-BB),platelet-derived growth factor AB (PDGF-AB), granulocyte-macrophagecolony-stimulating factor (GM-C SF), heparin, interleukin 8, thyroxine,or functional fragments thereof.

FIGS. 10A-10D illustrate endoprosthesis 10 covered by a sheath 1 thathas projections 16. The projections are attached to the sheath at oneend while the other end of the projection remains unattached. Whenplaced opposite the neck of the aneurysm, the projections 16 extend intothe neck of the aneurysm 12 and slow blood flow into the aneurysm. Thisreduced blood flow can cause a thrombosis and thus further reduce bloodflow into the aneurysm. Any projections not opposite the neck of theaneurysm will not extend but be caught between the sheath 1 and the wallof the blood vessel 14. The projections preferably between 0.5-5.0 mm inlength can be made of any thin, flexible material. Preferably, theprojections are longer than the diameter of any perforator vessel orartery in proximity to the aneurysm. In some embodiments, theprojections can be added to a central portion of another sheath of theinvention (e.g., as shown in any of FIGS. 1A-1B, 2A-2B, 3A-3B, 4A-4B,5A-5B, 9A-9B, and 11A-11B) to further slow blood flow. Such anembodiment is depicted in FIG. 10C where the projections are attached tothe polymer sheath of FIGS. 11A-11B.

FIG. 11A is a picture of an endoprosthesis 10 covered with a sheath 1wherein the central portion 5 has substantially the same permeability toblood flow as the outer portions 6. The sheath 1 is made of a polymerthat has a porosity in the range of 10-100 micrometers. Although thesheath is made of a substantially uniform material over its entirelength, the properties of the perforator vessels and aneurysm themselvesimpart a functional difference to the sheath. Areas opposite the sheaththat have an out-flow (such as perforator vessels) allow blood to flowthrough the sheath. Areas opposite the sheath with no out-flow (such asthe aneurysm) cause blood flow to be restricted through the sheath. FIG.11B shows a 500× magnification of the strands of the polymer that madeup the sheath in this embodiment. In addition to polymers, a sheath canbe made of any material capable of supporting 10-100 micrometers gaps orperforations. Optionally this sheath may, in the central portion, havean additional coating. This coating may comprise a biodegradable polymerand one or more agents which promote inflammation and/orthrombogenicity.

The contents of all published articles, books, reference manuals andabstracts cited herein, are hereby incorporated by reference in theirentirety to more fully describe the state of the art to which theinvention pertains.

As various changes can be made in the above-described subject matterwithout departing from the scope and spirit of the present invention, itis intended that all subject matter contained in the above description,or defined in the appended claims, be interpreted as descriptive andillustrative of the present invention. Modifications and variations ofthe present invention are possible in light of the above teachings.

1-40. (canceled)
 41. A device for treating an aneurysm comprising: anendoprosthetic device; and a sheath; wherein the sheath comprises acentral portion having a plurality of elongated flexible projectionsconnected directly thereto and outer portions that do not haveprojections, each projection having a first end attached to the sheathand a second end unattached, said projections having a length longerthan the diameter of any perforator vessel in proximity to said aneurysmthat permits extension of said projections into said aneurysm but notsubstantially into adjacent perforator vessels, such that blood flow tothe aneurysm is reduced while blood flow to a perforator vessel coveredby the device is substantially maintained.
 42. The device of claim 41,wherein the endoprosthetic device is a stent.
 43. The device of claim41, wherein the projections are between about 0.5 and 5.0 mm in length.44-48. (canceled)
 49. The device of claim 41, wherein the sheath is aporous polymer.
 50. The device of claim 41, wherein the projections areformed of a thin flexible material.
 51. The device of claim 41, whereinthe projections are hair-like.
 52. The device of claim 41, wherein thesheath extends over only a central portion of the endoprosthetic device.53. The device of claim 41, wherein the projections are oriented toextend along only a first side of the sheath.
 54. The device of claim53, wherein the projections extend along the sheath in a predeterminedlinear pattern.
 55. The device of claim 41, wherein the projections areconfigured such that a first portion thereof extends into the aneurysmand a second portion thereof remains external thereto, the secondportion of the projections configured to fold in response to pressureapplied thereto by walls of the perforator vessel.
 56. The device ofclaim 41, wherein the sheath is uniformly permeable.
 57. The device ofclaim 56, wherein the sheath is formed of a polymer with a porosity inthe range of 10-100 micrometers over its length.
 58. The device of claim41, wherein the projections are configured to cause thrombosis of theaneurysm.
 59. The device of claim 41, wherein at least one of the outerportions of the sheath is configured to face the one or more perforatorvessels or arteries.
 60. The device of claim 41, wherein said sheath iscoupled to said endoprosthetic device via an adhesive.
 61. The device ofclaim 60, wherein said sheath is configured to detach from saidendoprosthetic device after a predetermined length of time has elapsed.62. The device of claim 60, wherein said sheath is configured to detachfrom said endoprosthetic device upon application of a force exceeding apredetermined magnitude thereto.
 63. A device for treating an aneurysmcomprising: an endoprosthetic device; and a sheath; wherein said sheathcomprises a plurality of hair-like projections, each projection having afirst end attached to the sheath and a second end unattached, saidprojections having a length longer than the diameter of any perforatorvessel in proximity to said aneurysm that permits extension of saidprojections into said aneurysm but not substantially into adjacentperforator vessels.
 64. A device for treating an aneurysm comprising: anendoprosthetic device; and a sheath; wherein said sheath comprises aplurality of thin flexible projections, each projection having a firstend attached to the sheath and a second end unattached, and wherein saidprojections are between about 0.5 and 5.0 mm in length such that bloodflow to the aneurysm is reduced while blood flow to a perforator vesselcovered by the device is substantially maintained, said projectionsbeing configured such that a first portion thereof extends into theaneurysm and a second portion thereof remains external thereto, thesecond portion of the projections configured to fold in response topressure applied thereto by walls of the perforator vessel.